Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (Prior to GLP, only two dose groups)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
(only two dose groups)
Principles of method if other than guideline:
Dynamic inhalation method whereby rats were exposed nose and head only to dynamic concentrations of the test substance. Observation were made regarding clinical signs of toxicity and mortality over a period of 14 days. Moribund animals were sacrificed. Necrospy was performed on deceased animals and all sacrificed animals. LD 50 was determined based on mortality.
GLP compliance:
no
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Propionsaeure
- Batch number: 77/523
- Physical state: liquid
- Analytical purity: 100%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River France
- Age at study initiation: no data
- Weight at study initiation: 200 -300 g
- Fasting period before study: no data
- Housing: 2/cage (Makrolon type 3)
- Diet (e.g. ad libitum?): "Herilan MRH Haltungsdiaet", ad libitum
- Water (e.g. ad libitum?): tap water, ad libitum
- Acclimation period: > 7 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
nose/head only
Vehicle:
other: air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Kimmerle chambers with modified animals tubes
- Exposure chamber volume: 28.5 L
- Method of holding animals in test chamber: no data
- Source and rate of air: fresh air and 20 l/min
- Method of conditioning air: Air was filtered (c-filter)
- System of generating vapour: cylindrical high grade steel vaporizer: heating coil surrounding the heating cartridge. The test substance is transported to the heating coil via high grade steel capillaries on the heating cartridge. Dosing of the test substance is performed with an infusion pump.
- Method of particle size determination: no
- Treatment of exhaust air: no data
- Temperature, humidity: 21-23°C, 60-63%


TEST ATMOSPHERE
- Brief description of analytical method used: The test substance is aspirated using a graduated wash bottle which contains 40ml NAOH (1N). After aspiration, the aspiration outlet is rinsed with 10 ml 1N NaOH. Aspiration was performed at a rate of 0.5 l/min, a speed of 1.18 m/s and for duration of 5 min. After neutralisation with H2SO4, the concentration of the test substance was determined by GC (FID)
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:
yes
Remarks:
GC (FID)
Duration of exposure:
1 h
Concentrations:
2.69 and 19.7 mg/l
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (clinical signs and mortality): < 15 min, 15 min, 30 min, 1h, 2h, 4h, 5h and then daily till day 14
- Frequency of weighing: immediately before exposure, 7 d and 14 days post exposure
- Necropsy of deceased animals performed: yes
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 19.7 mg/L air
Exp. duration:
1 h
Remarks on result:
other: 1/10 female animal died
Mortality:
- 2.69 mg/l: no mortality
- 19.7 mg/l: 1 female animal died in the observation period
Clinical signs:
During exposure
- 2.69 mg/l (both sexes): slightly constricted palpebral fissure (closed eyes), wet fur (from urine) and slight tearing
- 19.7 mg/l/ (both sexes): reduced respiratory frequency, slight to increased intermittent respiration, tightly closed eyes, slight tearing, slight to heavy salivation, slight to heavy nasal secretion, slight corneal opacity.
During Observation period:
- 2.69 mg/l: wet fur coat. No symptoms were manifested as from 4h post exposure
- 19.7 mg/l: intermittent respiration, tightly closed eyes, nasal swelling. In males only; irreversible corneal opacity (still present in one rat on day 14). In females only: slight reduced respiration rate. Corneal opacity lasted only 24 hours after end of exposure.
Body weight:
- 2.69 mg/l: weight gain factor for the first and second week were 1.21 and 1.1, for males and 1.1 and 1.1 for females, respectively
- 19.7 mg/l: weight gain factor for the first and second week were 1.21 and 1.1 for males and 1.1 and 1.0 for females, respectively
Gross pathology:
- Deceased animal: gray-pinkish colouring of the lungs, intestines were filled with gas, emphysematous and partly atelectatic lungs
- Sacrificed animals: in the high dose group, multiple petechiae in 4/19 rats

Applicant's summary and conclusion